Humanized antibodies

Abstract

The present disclosure provides humanized antibodies, including antibodies comprising an ultralong CDR3 and uses thereof.

The invention claimed is: 
     
       1. A humanized antibody or binding fragment thereof comprising a variable heavy chain comprising an ultralong CDR3 in which the CDR3 is replaced by a CDR3 scaffold which is 45 amino acids in length or longer and comprises a X 1 X 2 X 3 X 4 X 5 Xn(X a X b )z motif,
 wherein the X 1 X 2 X 3 X 4 X 5  motif is TTVHQ (SEQ ID NO:153) or TSVHQ (SEQ ID NO:154), 
 wherein, for X n , X is any amino acid and n is 27-54, and 
 wherein the (X a X b ) z  motif is YXYXYX with X being any amino acid. 
 
     
     
       2. The humanized antibody or binding fragment thereof of  claim 1 , wherein the ultralong CDR3 is 50 amino acids in length or longer. 
     
     
       3. The humanized antibody or binding fragment thereof of  claim 1 , wherein the ultralong CDR3 comprises 3 or more cysteine residues. 
     
     
       4. The humanized antibody or binding fragment thereof of  claim 1 , wherein the ultralong CDR3 comprises:
 a non-human VH sequence or a derivative thereof; 
 a non-human DH sequence or a derivative thereof; and/or 
 a JH sequence or derivative thereof. 
 
     
     
       5. The humanized antibody or binding fragment thereof of  claim 1 , wherein the ultralong CDR3 comprises a non-bovine sequence or a non-antibody sequence. 
     
     
       6. The humanized antibody or binding fragment thereof of  claim 1 , wherein the humanized antibody or binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 461, 462, 463, 464, 465, 466, 467, 468, or 469 and the amino acid sequence set forth in SEQ ID NO: 470. 
     
     
       7. A library of humanized antibodies or binding fragments thereof, wherein the library comprises antibodies or binding fragments thereof of  claim 1 . 
     
     
       8. The humanized antibody or binding fragment thereof of  claim 5 , wherein the non-antibody sequence is a cytokine sequence, a lymphokine sequence, a chemokine sequence, a growth factor sequence, a hormone sequence, or a toxin sequence. 
     
     
       9. The humanized antibody or binding fragment thereof of  claim 5 , wherein the non-antibody sequence is an IL-8 sequence, an IL-21 sequence, an SDF-1 (alpha) sequence, a somatostatin sequence, a chlorotoxin sequence, a Pro-TxII sequence, or a ziconotide sequence. 
     
     
       10. The humanized antibody or binding fragment thereof of  claim 5 , wherein the ultralong CDR3 comprises an additional linker sequence, wherein the linker is linked to a C-terminus, a N-terminus, or both C-terminus and N-terminus of the non-antibody sequence. 
     
     
       11. The humanized antibody or binding fragment thereof of  claim 1 , wherein the humanized antibody or binding fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 461, 462, 463, 464, 465, 466, 467, 468, or 469; the amino acid sequence set forth in SEQ ID NO:470; and a peptide sequence, wherein the peptide sequence is positioned between SEQ ID NO: 461, 462, 463, 464, 465, 466, 467, 468, or 469, and SEQ ID NO: 470. 
     
     
       12. The humanized antibody or binding fragment thereof of  claim 1 , wherein the humanized antibody or binding fragment comprises a light chain variable region sequence that is a lambda light chain variable region sequence. 
     
     
       13. The humanized antibody or binding fragment thereof of  claim 11 , wherein the humanized antibody or binding fragment comprises a light chain variable region sequence that is a lambda light chain variable region sequence.